Tertiary amines containing the 1-amino-2-hydroxypropyl residue



- Patented Jan. 27, 1931 I UNITED- T T-Es ATEN orrlcs j HEINRICH JENSCH,or HooHs'r-oN-rHE-Mmn, GERMANY, AssIeNon r0 wm'rnn'or CHEMICAL COMPANYme, on NEW YORK, n, Y.,-A CORPORATION a 1 TERTIARY'AMiNES con'rarnme rnni-arrrnoensmnoxxrnoryr. nnsrnnn No Drawing; Application filed. July as,1927, Serial No. 208,060, and a Germany'Aug'us't is, 1926.

My present invention relates to tertiary amines containing thel-amino-Q-hydroxypropyl residue and to a process of preparing the same.

V I have found that the hitherto unknown I tertiary amines of thegeneral formula 1 nitrogen containing nucleus, can be prepared bycauslng secondary 2111111165 to act :upon' 3-halogen-2hydroxypropylamine salts (see Berichte der Deutschen Chemischen Gesell-,.schaft, volume 50, page 822). Instead of using the8-halogen-2-hydroxypro-pylamine,

salts obtained by saponification of 3-halogen-2-hydroxypropylphthalimide it is also possible to cause the secondaryamines to act upon 3 halogen 2-hydroxypropylphthalimide (see Berichte,volume 50,.pages 820,

821 and S25) and then split off-the phthalic acid residue; The newtertiary amines are separted by means of an alkali and purifiedlay-distillation. They are of therapeutical value and have a blood-sugarreducing action, belng at the same time useful as intermediate productsfor the manufacture of other medicines.

my invention, but-they are not intended to "boiling 'in a. refluxapparatus for several hours. After'having distilled 01f the alcohol, theresidue is boiled for about three hours with hydrochloric acid of 2-0per cent.

which has separated is filtered ofi, the filtrate is concentrated andthe u-amino-B-hydroxy- -diethylaminopropane is separated as an oil bythe addition of strong caustic potash solution. This oil is separatedfrom the aqueous layer and distilled'in a vacuum. It is thus obtained asa colorless oil of a slightly basic smell boiling at 114 C. to 115 C.under 20 29 g. ofthe hydrochloride of 3- chloro- 2-hydroxypropylamineareheated to boiling formula: strength; after cooling, the phthalic acid 1mm. pressure. Its hydrochloride is extremely for several hours withg3 lg-.'of diethylamine and 100 com. of alcohol. After having distilled offthe alcohol, there is added to they;

residue a strong causticpotash solution the whole is thenheated for sometnnefin order to expel the d1ethylam1ne,the remainmg oil-1s separatedand distilled in vacuo. Thus the 3 diethylamino-2-hydroxypropylamineis'ob-i- 'tained having the properties fdescribed' in Example 1'."

3. 130 g. of 3-chloro .2-hydroxyproplphthalimide are heated in a steambomb for 4 hours with 175 of an alcoholic dimethyl-- amine solutionof30' per cent strength. The 7 contents of the bomb is then concentratedby evaporating, the remaining sirupy mass is boiled for 4 hours with 750com. of hydroch1oric acid of 20 per cent. strength; after cooling, thesolution is separated from the phthal-.

io acid and evaporated in a vacuum until it is thick like sirup. A Thissirupymass is mixed first with: concentrated caustic soda solution andthen with potassium carbonate until a thick magma is obtained'which. isrepeatedly digested with benzene. After having dried these extracts bymeans of pot'assiumcarbonate,they are freed from the benzene and theresidue is distilled in aivacuum. The new;

:. baseboils .under'28 mm. pressure at 103 C.

It is a colorless oiliofabasicsmelland yields a solidhydrochloridewhichis, however, ex-

remely hygroscopic. It has the probable I V l i cm F H*- B -QHz-N i 4.80 g. a e-b161 5:agii drbizypro lphthalimide and -60 g]. of'piperidinein 200 com. of alcohol are treated as indicated in Exobtainedboilingnnder 29 pressure at I solution of the base with alcoholichydrochloric acid, the Colorless dihydrochloride is obtained as aviscous mass which gradually solidifies and melts afterrecrystallizationfrom absolute alcohol at 181 C. It is very easilysoluble in water. Theproduct obtainable according to this example hasthe probable formula .. H Hi 7 5; 80 g. of 3chloro-2-'hydroxyproylphthalimide are treated as above indicated with 71g. of monomethylaniline. After having split off the phthaloyl residue,filtered the phthalic acid and evaporated the filtrate,the remainingmass .is neutralized with concentrated caustic soda solution; there isthen added-thereto a saturated potassium carbonate solution and the baseis shakenv out with chloroform. The residue of the chloroform solutionis fractionated in a vacuum. The base is thus obtained in the form of aslightly yellow oil which distils over under 30 mm. pressure at between205 C. and 210 .C. and solidifies into a. colorless mass. It is readilysoluble in chloroform, less soluble in benzene and diflicultly solublein cold ether. 7 When recrystallized from ether itv melts at 71 C. Itgives a colorless hydrochloride which is very readily soluble in waterand melts on recrystallization from absolute alcohol at 201 C. whilefoaming. It has'the probable formula: V

V CH3 mN.oHLcmoHyoHafIjofiHa I-claimi 1. As a new product, l-amino-3-dimethylr amino-Q-propanol of the formula: g 1 CH3HzN.OHn.CH(OH).CHz.N

being a colorless oily base which forms readily-water-s oluble salts andboiling under 28 mm. pressureat 103 C. V

2. The process which comprises causing a secondary amine to act upon acompound of the general formula N.om.oH om.oH2.Ha1

wherein Hal represents a halogen atom, Z and Z stand for hydrogen orjointly for the phthalic acid residue /oonii n 3. The process whichcomprises causing a secondary amine to act upon 3-halogen-2-hydroxypropyl-phthalimide 'of the formula A oo 1 wherein Hal representsa halogen atom, and

splitting off the'phthalic acid residue.

- 5. As new products the compounds of the 7 general formula carbon atomsbelonging to a heterocyclic nitrogen containmg nucleus, the saidcompounds being-substances of a high basicity which form with acidsreadily soluble salts and which are distinguished by a blood-sugarreducing action.

6. As new products the compounds of the. general formula wherein Nrepresents "nitrogen of a tertiary amine, X stands for an alkyl-groupand Y stands for an alkyl-v or phenyl-group,;the said compounds beingsubstancesof a high basicity which form with acids readily soluble saltsand which are distinguished by a bloodsugar reducing action.

7. As new products the compounds of the general formula wherein Nrepresents nitrogen of a tertiary soluble salts andfwhich aredistinguished by a blood-sugar reducing action.

In testimony whereof I affix my signature.

HEniRIoH .JENSOH.

